Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8P19W2)

DOT Name	Transcription factor HES-1 (HES1)
Synonyms	Class B basic helix-loop-helix protein 39; bHLHb39; Hairy and enhancer of split 1; Hairy homolog; Hairy-like protein; hHL
Gene Name	HES1
Related Disease	Acute kidney injury ( ) Hepatocellular carcinoma ( ) Meningioma ( ) Acute myelogenous leukaemia ( ) Breast cancer ( ) Breast carcinoma ( ) Cervical cancer ( ) Colon cancer ( ) Colon carcinoma ( ) Colonic neoplasm ( ) Colorectal carcinoma ( ) Intracranial meningioma ( ) Lung neoplasm ( ) Lymphangioleiomyomatosis ( ) Medulloblastoma ( ) Neoplasm ( ) Primitive neuroectodermal tumor ( ) Uterine cervix neoplasm ( ) Breast neoplasm ( ) Epilepsy ( ) Advanced cancer ( ) Glioblastoma multiforme ( ) Lung cancer ( ) Non-small-cell lung cancer ( )
UniProt ID	HES1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2MH3; 7C4O
Pfam ID	PF07527 ; PF00010
Sequence	MPADIMEKNSSSPVAATPASVNTTPDKPKTASEHRKSSKPIMEKRRRARINESLSQLKTL ILDALKKDSSRHSKLEKADILEMTVKHLRNLQRAQMTAALSTDPSVLGKYRAGFSECMNE VTRFLSTCEGVNTEVRTRLLGHLANCMTQINAMTYPGQPHPALQAPPPPPPGPGGPQHAP FAPPPPLVPIPGGAAPPPGGAPCKLGSQAGEAAKVFGGFQVVPAPDGQFAFLIPNGAFAH SGPVIPVYTSNSGTSVGPNAVSPSSGPSLTADSMWRPWRN
Function	Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity. May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.
KEGG Pathway	Fanconi anemia pathway (hsa03460 ) Notch sig.ling pathway (hsa04330 ) Maturity onset diabetes of the young (hsa04950 ) Human papillomavirus infection (hsa05165 ) Epstein-Barr virus infection (hsa05169 ) Pathways in cancer (hsa05200 ) Breast cancer (hsa05224 )
Reactome Pathway	NOTCH1 Intracellular Domain Regulates Transcription (R-HSA-2122947 ) NOTCH2 intracellular domain regulates transcription (R-HSA-2197563 ) Constitutive Signaling by NOTCH1 PEST Domain Mutants (R-HSA-2644606 ) Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants (R-HSA-2894862 ) RUNX2 regulates osteoblast differentiation (R-HSA-8940973 ) RUNX3 regulates NOTCH signaling (R-HSA-8941856 ) NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508 ) NOTCH4 Intracellular Domain Regulates Transcription (R-HSA-9013695 ) Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells (R-HSA-210744 )

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Acute kidney injury	DISXZG0T	Definitive	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[2]
Meningioma	DISPT4TG	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Colon cancer	DISVC52G	Strong	Biomarker	[7]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[7]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[9]
Intracranial meningioma	DISD09EF	Strong	Biomarker	[3]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[10]
Lymphangioleiomyomatosis	DISR0RNB	Strong	Biomarker	[11]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Altered Expression	[13]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[3]
Uterine cervix neoplasm	DIS0BYVV	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[14]
Epilepsy	DISBB28L	moderate	Therapeutic	[15]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[16]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[17]
Lung cancer	DISCM4YA	Limited	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[19]
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⏷ Show the Full List of 24 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Transcription factor HES-1 (HES1).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription factor HES-1 (HES1).	[49]
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48 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor HES-1 (HES1).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor HES-1 (HES1).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transcription factor HES-1 (HES1).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Transcription factor HES-1 (HES1).	[24]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor HES-1 (HES1).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transcription factor HES-1 (HES1).	[26]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Transcription factor HES-1 (HES1).	[27]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Transcription factor HES-1 (HES1).	[28]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transcription factor HES-1 (HES1).	[29]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor HES-1 (HES1).	[30]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transcription factor HES-1 (HES1).	[31]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Transcription factor HES-1 (HES1).	[32]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Transcription factor HES-1 (HES1).	[33]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transcription factor HES-1 (HES1).	[34]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Transcription factor HES-1 (HES1).	[35]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Transcription factor HES-1 (HES1).	[36]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Transcription factor HES-1 (HES1).	[32]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the activity of Transcription factor HES-1 (HES1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Transcription factor HES-1 (HES1).	[38]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transcription factor HES-1 (HES1).	[39]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the activity of Transcription factor HES-1 (HES1).	[8]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Transcription factor HES-1 (HES1).	[40]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Transcription factor HES-1 (HES1).	[41]
Mebendazole	DMO14SG	Approved	Mebendazole decreases the expression of Transcription factor HES-1 (HES1).	[42]
PF-03084014	DMUP5Z0	Approved	PF-03084014 decreases the expression of Transcription factor HES-1 (HES1).	[41]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transcription factor HES-1 (HES1).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor HES-1 (HES1).	[44]
Triptolide	DMCMDVR	Phase 3	Triptolide decreases the expression of Transcription factor HES-1 (HES1).	[45]
Glycyrrhizin	DM8M2N3	Phase 3	Glycyrrhizin decreases the expression of Transcription factor HES-1 (HES1).	[46]
Avastin+/-Tarceva	DMA86FL	Phase 3	Avastin+/-Tarceva decreases the expression of Transcription factor HES-1 (HES1).	[40]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transcription factor HES-1 (HES1).	[47]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Transcription factor HES-1 (HES1).	[48]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Transcription factor HES-1 (HES1).	[36]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN increases the expression of Transcription factor HES-1 (HES1).	[39]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transcription factor HES-1 (HES1).	[50]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transcription factor HES-1 (HES1).	[51]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transcription factor HES-1 (HES1).	[52]
Baicalin	DMY1TLZ	Terminated	Baicalin increases the expression of Transcription factor HES-1 (HES1).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor HES-1 (HES1).	[53]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transcription factor HES-1 (HES1).	[54]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transcription factor HES-1 (HES1).	[55]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Transcription factor HES-1 (HES1).	[56]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Transcription factor HES-1 (HES1).	[57]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Transcription factor HES-1 (HES1).	[58]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Transcription factor HES-1 (HES1).	[59]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug decreases the expression of Transcription factor HES-1 (HES1).	[11]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of Transcription factor HES-1 (HES1).	[61]
aconitine	DMFOZ60	Investigative	aconitine increases the expression of Transcription factor HES-1 (HES1).	[62]
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⏷ Show the Full List of 48 Drug(s)

References

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36	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
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60	Mammalian target of rapamycin regulates murine and human cell differentiation through STAT3/p63/Jagged/Notch cascade. J Clin Invest. 2010 Jan;120(1):103-14. doi: 10.1172/JCI37964. Epub 2009 Dec 28.
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